Trace Metal Deficiency Research Articles

Enamel hypoplasia of the primary dentition in a 4‐year‐old with intestinal lymphangiectasia

Intestinal lymphangiectasia (IL) is a rare disorder, and its incidence and prevalence is unknown for either Australia or world-wide. It is characterized by diarrhoea, mild steatorrhoea, oedema, enteric loss of protein (protein-losing enteropathy) and abnormal dilated lymphatic channels in the small intestine. Whilst oedema and diarrhoea are the predominant clinical features, other observed features include hypoalbuminemia, hypogammaglobulinemia, trace metal deficiency, hypocalcemia and chylous pleural effusions. While medical presentation of the condition has been reported widely, few descriptions of oral findings have been published. A search of Medline found two reports of dental findings in the permanent dentition in patients with IL. To date, there have been no reports on dental findings in the primary dentition. The primary dentition of a 4-year-old boy with IL had teeth with enamel defects which reflected the timing of enamel development and the period in which the disease was active. The present report highlights the need for early involvement of the dental team in the dental management of children with IL.

The effect of ryegrass variety on trace metal uptake

Trace metal deficiencies in soils can have adverse effects on plant production and animal health. Conversely, trace metals at elevated concentrations in soils can be phytotoxic. The exploitation of intraspecies variation in plant trace metal accumulation may be one way to manage both trace metal deficiency and phytotoxicity that can occur in some soils. An investigation was undertaken to determine the variation in Co, Cd, Ni, Cu, Zn, Mn, and Fe uptake in different ryegrass varieties. Eleven different ryegrass varieties were grown in a glasshouse experiment on two soils that contained elevated or background metal concentrations. We found that there was up to a 2.5‐fold range in trace metal concentrations between ryegrass varieties grown on the contaminated soil, with the short rotation/annual ryegrass varieties, i.e., ‘Flanker’, ‘Tabu’, and ‘Archie’, generally accumulating significantly smaller amounts of Cd, Zn, Ni, Mn, and Co than the other varieties tested. Metal uptake in the uncontaminated soil indicated much smaller differences between varieties. Dilution effects could in part explain the differences in metal concentrations between varieties for the contaminated soil, however there were no relationships between yields and trace metal concentrations for uncontaminated soil. It appears that there may be potential for selecting ryegrass varieties for the management of trace metal uptake in pasture soils, however further evaluation of results in field trials is required.

Vitamin and trace metal levels in recessive dystrophic epidermolysis bullosa.

In recessive dystrophic epidermolysis bullosa (RDEB), a good nutritional balance is necessary to obtain healing of the chronic wounds. However, involvement of the oral mucosa and oesophagus stenosis may be responsible for severe nutritional deficiencies. In order to propose an adapted nutritional management, we studied the vitamin and trace metal status of 14 RDEB patients. Height and weight were measured. Plasma levels of albumin, iron, ferritin, calcium, parathyroid hormone (PTH), folates, vitamins C, D, B12, A, E, B1, B6, PP and B2, zinc, selenium, carnitine and copper were measured. Most patients had a significant growth retardation. We found iron, vitamin D, C, B6, PP, zinc and selenium deficiencies in 36-70% of the patients, without clinical expression, except in one case. Vitamin B1, 12, B2, A/RBP, E/lipids and carnitine were normal. The three patients with gastrostomy feeding had better growth but still a protein deficiency and sometimes vitamin C, B6, PP, zinc and carnitine deficiencies. Vitamin and trace metal deficiencies are frequent in RDEB, even in patients receiving gastrostomy feeding, and often go unrecognized. Regular nutritional evaluation is necessary. Dietary advice and supplements should be given. Enteral feeding by gastrostomy should be discussed in early childhood.

Wasted sheep and premature infants: the role of trace metals in hematopoiesis

Trace element deficiencies and toxicities are not commonly encountered in clinical practice, particularly in regions where there is access to adequate nutrition and occupational exposures are regulated. However, specific clinical scenarios associated with trace metal deficiency and toxicity states do exist. Often, clues to the presence of these states may lie in the development of blood count abnormalities. The consultant haematologist is frequently involved in the care of these patients, and it is with this audience that this review is intended. This review will focus on the trace metals required for normal hematopoiesis including their function, metabolism, deficiency and toxicity states, and the clinical situations underlying these. As much of the information regarding trace metal disease states has arisen from veterinary medicine and from human case reports, these will be summarized and highlighted in this review.

Pica and Trace Metal Deficiencies in Adults with Developmental Disabilities

(1999). Pica and Trace Metal Deficiencies in Adults with Developmental Disabilities. The British Journal of Development Disabilities: Vol. 45, No. 89, pp. 111-117.

Bone growth and bone development in the presence of implants or after induced leg-lengthening studied using the Oxford Scanning Proton Microprobe

To respond to varying environmental demands the bone tissue in the body is under continual reconstruction throughout life. It is known that metallic elements are important for maintaining normal bone structure, but their roles are not well understood. More information about the effects of metal excess or deficiency is needed to help in the development of metallic bone implants and to improve the treatment of bone fractures and defects. The Oxford Scanning Proton Microprobe (SPM) is being applied in two studies involving metal ions in bone: (1) bone regrowth and bonding to titanium bone implants may be influenced by diffusion of Ti ions into the bone. We are using microPIXE to determine the metal ion content of bone developing in contact with implants of pure Nb, Ti and Ti alloys. (2) Bone lengthening as a surgical procedure is induced by fracturing the bone and allowing it to heal with a small gap between the fractured ends created by the use of external fixators. The gap can be slowly increased during the healing process to stimulate the production of new bone. The enzymes and other constituents of the developing bone need certain metals for their function. Using experimental animals we have studied the concentrations of the metals and whether a deficiency of trace metals limits the optimum rate of bone lengthening.

Phytosiderophore release in relation to micronutrient metal deficiencies in barley

Phytosiderophore release occurs under both iron and zinc deficiencies in representative Poaceae and has been speculated to be a general adaptive response to enhance the acquisition of micronutrient metals. To test this hypothesis, phytosiderophore (PS) release rates from barley (Hordeum vulgare cv. CM72) subjected to deficiencies of Fe, Zn, Mn, and Cu were compared using chelator-buffered nutrient solutions. PS release rates were determined at two day intervals during onset and development of deficiency symptoms. Plant dry matter yields and nutrient concentrations, measured at three time points were used to construct growth curves for calculation of PS release per unit root mass and estimation of critical internal nutrient levels associated with PS release. In comparison to trace metal-sufficient control plants, dry matter production was markedly reduced in the Zn, Mn, and Cu deficiency treatments, with final relative yields of 49, 61, and 34%, respectively. Relative yields for Fe-deficient plants grown at three suboptimal Fe levels ranged from 95 to 33% of control, and provided a basis for comparison of PS release rates by Zn-, Mn-, and Cu-deficient plants at similar levels of growth inhibition. Under Fe deficiency, PS release increased with severity of the deficiency as measured by foliar Fe concentration, yield reduction, and chlorosis. Changes in PS release rates over time suggested a cyclical pattern that may be regulated by Fe concentration in the plant shoot. The highest rate of PS release (35 μmol g−1 root dw 2 h−1) was measured after 10 days of growth at pFe 19, whereas control plants adapted for growth at pFe 17 released only 2 to 3 μmol g−1 root dw 2 h−1. In a second experiment, maximum PS release rates for barley subjected to Zn, Mn, and Cu deficiencies were only 2.6, 2.5 and 1 μmol g−1 2 h−1, respectively and were only slightly elevated over those of the control plants (ca. 1 μmol g−1 root dw 2 h−1) grown at pFe 16.5. Moreover, enhanced PS release under Zn deficiency occurred much later, after the deficiency had already caused severely reduced growth. The results suggest that phytosiderophore release in this barley cultivar is a specific response to Fe deficiency and is not significantly induced in response to deficiencies of other trace metals.

Factors controlling phytoplankton ice-edge blooms in the marginal ice-zone of the northwestern Weddell Sea during sea ice retreat 1988: Field observations and mathematical modelling

The factors controlling phytoplankton bloom development in the marginal ice zone of the northwestern Weddell Sea were investigated during the EPOS (Leg 2) expedition (1988). Measurements were made of physical and chemical processes and biological activities associated with the process of ice-melting and their controlling variables particularly light limitation mediated by vertical stability and ice-cover, trace metal deficiency and grazing pressure. The combined observations and process studies show that the initiation of the phytoplankton bloom, dominated by nanoplanktonic species, was determined by the physical processes operating in the marginal ice zone at the time of ice melting. The additional effects of grazing pressure by protozoa and deep mixing appeared responsible for a rather moderate phytoplankton biomass (4 mg Chla m−3) with a relatively narrow geographical extent (100–150 km). The rôle of trace constituents, in particular iron, was minor. The importance of each factor during the seasonal development of the ice-edge phytoplankton bloom was studied through modelling of reasonable scenarios of meteorological and biological forcing, making use of a one-dimensional coupled physicalbiological model. The analysis of simulations clearly shows that wind mixing events — their duration, strength and frequency — determines both the distance from the iceedge of the sea ice associated phytoplankton bloom and the occurrence in the ice-free area of secondary phytoplankton blooms during the summer period. The magnitude and extent of the ice-edge bloom is determined by the combined action of meteorological conditions and grazing pressure. In the absence of grazers, a maximum ice-edge bloom of 7.5 mg Chla m−3 is predicted under averaged wind conditions of 8 m s−1. Extreme constant wind scenarios (4–14 m s−1) combined with realistic grazing pressure predict maximum ice-edge phytoplankton concentrations varying from 11.5 to 2 mg Chla m−3. Persistent violent wind conditions (≥ 14 m s−1) are shown to prevent blooms from developing even during the brightest period of the year.

Some modifications in trace metal toxicities and deficiencies in plants resulting from interactions with other elements and chelating agents‐‐the special case of iron

Abstract Whenever land becomes contaminated with trace metals, most always two or more of the trace metals are in excess simultaneously. Nearly all of the baseline studies of metal excesses, however, have been made with single metals, and such studies do not accurately reflect the critical response levels. Various critical points can shift due to interactions. Analytical data must be obtained for as many as 20 different elements and their differential distribution among various plant parts, including roots, must be known to gain even a partial understanding of the interactions. Positive and negative synergisms, competition, protection, and sequential additivity are observed among the interactions. The nature of interactions varies considerably with concentration levels, soil pH, soil texture, level of soluble Ca in soil, presence of salinity, differential distribution in soil of the metals present in toxic quantities, presence or absence of chelating agents, soil organic matter levels, and other factors. Interactions are difficult to model. All of these relate to the behavior of Fe in plants and in soil. Iron deficiency is commonly induced by excess levels of other trace metals, both singly and more commonly in various combinations. Such Fe deficiency is complex. Other essential nutrients are involved in somewhat similar interactions. When testing soil for possible problems with Fe deficiency, it is important that concentrations of available trace elements other than Fe in addition to other soil parameters be considered in the equation for prediction.

Induction of skeletal malformations in the offspring of rats fed a zinc deficient diet.

Pregnant rats were subjected to a trace metal poor diet (1.2 ppm zinc, 5.9 ppm copper, 40 ppm manganese) during the entire gestation. The rat mothers did not gain weight during pregnancy and showed decreased liver weight and lowered serum glucose levels on gestational day 20. The offspring exhibited decreased body and placental weights, delayed ossification of the skeleton, and an increased resorption rate. We also found 4% skeletal malformations in the offspring (0% in the controls), which closely resembled a type of malformation previously encountered in rats when the mother was manifest diabetic (i.e. sacral dysgenesis). The zinc levels were decreased and manganese levels increased to the same extent in offspring of trace metal restricted (this study) and manifest diabetic rats (previous studies). Furthermore, when pregnant rats on the trace metal restricted diet were resupplemented with 75 ppm zinc in the drinking water the offspring largely normalized their somatic and placental growth, skeletal maturation, as well as their zinc and manganese levels. In addition, the fetuses of the zinc resupplemented rats did not show any malformations. The possibility of common teratological mechanisms in maternal diabetes and trace metal deficiency may therefore be considered.

Genetic trace metal disturbances.

Genetic trace metal disturbances can be at three levels. Trace metals play an important role in the metabolism of genetic macromolecules and the information transfer system. Deficiency or excess of trace metals caused either by dietary or genetic factors will affect the normal functioning of the whole organism. The roles of trace metals in carcinogenesis/mutagenesis and ageing are typical of this category. The second level of genetic trace metal disturbances affect the metabolic pathway of the trace metal itself. Biochemical derangement resulting from genetic defects cause aberrant metabolism of the element and thus disease symptoms. Diseases caused by abnormal metabolism of copper, zinc, iron, and molybdenum are discussed. Trace metal disturbances can also be the result of other genetic diseases. This aspect of genetic trace metal disturbances is least investigated. However, information should be important for improving the existing treatment protocol for the more common inborn errors of metabolism, such as phenylketonuria.

Nutritional Aspects of Down's Syndrome with Special Reference to the Nervous System

Multiple deficiencies of vitamins and trace metals have been demonstrated in Down's syndrome. The picture is complex, especially since not all individuals are affected equally. Deficiencies are not age-related, but appear to be lifelong. The brain in Downs's syndrome does not develop adequately; one area, the hippocampus, which is concerned with memory, is poorly developed and is also involved in the pathological changes of Alzheimer's disease. The role of nutrients is discussed in relation to damage to the mature brain, and to the ageing process.

Measurement of superoxide dismutase, diamine oxidase and caeruloplasmin oxidase in the blood of thoroughbreds

Methods were developed for the measurement of superoxide dismutase (SOD), diamine oxidase (DAO) and caeruloplasmin oxidase in the blood of thoroughbred horses. These enzymes were measured in 178 normal thoroughbreds stabled throughout the United Kingdom. The relationships between the activities of SOD, DAO and caeruloplasmin oxidase and the blood concentrations of their associated trace metals (copper, zinc and manganese) were studied in 52 of the thoroughbreds. Trace metals were measured by electrothermal atomic absorption spectrophotometry. No relationships were found between the activities of erythrocyte SOD and serum/whole blood copper, zinc and manganese, or serum DAO and serum copper or zinc concentrations. Caeruloplasmin oxidase in equine blood was found to be correlated to serum copper concentration, r = 0.695 (P less than 0.001) over the normal range. Samples from thoroughbreds with trace metal deficiency or toxicity were not available for study. The observed normal ranges for the activity of these enzymes are as follows: SOD: 50 to 200 units per ml whole blood between 5 and 95 percentiles; DAO: 0.1 to 28.5 units per litre (means = 14.8, SD 7.1) and caeruloplasmin oxidase; 11.6 to 35.8 units per ml (means = 23.7, SD 6.0). For numerical simplicity, the activity of DAO is given in units per litre, compared to units per ml for caeruloplasmin oxidase and SOD.

Some nutritional aspects of trace metals.

A brief outline of the known biochemical roles of manganese and chromium is given before the problems of determining human trace metal status are discussed. The factors predisposing to trace metal deficiency are reviewed but particular emphasis is placed upon those which alter the bioavailability of essential trace metals from natural and synthetic diets. This is illustrated by practical examples which show the importance of investigating the bioavailability of the trace metal content of artificial diets used in paediatric care. The results of such studies highlight the need to assess similarly the adequacy of the trace element composition of the many meat substitutes and extenders available currently. Finally, some aspects of trace metal supplementation of intravenous feeding regimens are described.

Anaerobic digestion of spent coffee grounds

Anaerobic digestion of spent coffee grounds (3 kg m −3 day −1) with efficient solids recycling achieved 99% conversion of solids and gas yields of 0·54 m 3 kg −1 (56–63% methane). Gas production declined steadily over the test period and after 80 days had fallen from an initial value of 1·70 litre litre −1 day −1 to 0·45 or 0·33 litre litre −1 day −1, with or without nitrogen supplementation respectively. Declining gas flows were not accompanied by other usual symptoms of digester failure and were not due to deficiency of nitrogen, phosphorus or trace metals. Inhibited digester liquors contained an unidentified component which inhibited gas production by fresh digestion liquors. This component was not a heavy metal, caffeine or brown ‘melanoid’ pigments. Digestion liquors could not be adapted to overcome this inhibition.

Removal of Trace Metals from Culture Media and Sera for In Vitro Deficiency Studies

Culture media and sera contain substantial quantities of trace metals such as zinc and copper, so that they cannot be used for cell culture studies of trace metal deficiencies unless the element in question is first removed. By coupling the chelator iminodiacetate to an insoluble agarose matrix, we have been able to extract zinc selectively from both media and sera, without exposing cells directly to the chelator. The procedure reduced the zinc concentration of media to unmeasurably low levels, and serum zinc concentration by approximately 90%. The development of zinc deficiency in vitro was demonstrated by a reduced lymphocyte blastogenic response, which could be prevented by the addition of zinc to the extracted culture medium. The extraction procedure is potentially applicable to a range of trace metals (e.g., Zn, Cu, Mn, Fe) and to virtually any cell type that can be cultured.trace metals zinc copper cell cultures

Mineral metabolism in the aging and the aged.

With the development of accurate and precise techniques for quantifying sodium, potassium, calcium, and magnesium concentrations, a vast literature has been generated indicating that deficits and excesses of these cations in the body create many clinical challenges for the physician. Iron has received its share of attention as the most abundant trace metal in the body, primarily being utilized in the formation of hemoglobin. Zinc is the next most abundant trace element in the body, and evaluation of its role in the biochemistry and pathophysiology of disease is now stimulating a great deal of interest. Deficiencies of the other trace metals also are receiving increasing attention as attempts to evaluate their importance in human nutrition are being made. Studies were not considered reliable until technological advances made it possible, by atomic absorption spectroscopy, neutron activation analysis, and other techniques, to quantify these trace elements accurately and precisely.

Trace metal abnormalities in adults during hyperalimentation.

Trace metal deficiencies are now a well-documented complication of total parenteral nutrition (TPN). Zinc deficiency may present in a variety of ways including acrodermatitis skin lesions, impaired immunity, poor growth or impaired wound healing, and mental disturbances. Copper deficiency presents a more uniform picture of hematologic abnormalities, usually anemia with leukopenia and neutropenia. Chromium and selenium deficiencies occur much less frequently, but well-documented cases have been reported. We currently recommended regular monitoring and supplementation of these four trace metals during TPN administration. This article describes the clinical abnormalities that may develop when deficiencies of trace metals occur during TPN administration, and we present recommendations for trace metal supplementation during TPN administration.

1275 EPIDEMIOLOGY OF ADVERSE REACTIONS TO TOTAL PARENTERAL NUTRITION (TPN)

To determine the magnitude of the risks in TPN delivered via peripheral vein, the incidence of adverse reactions to TPN was evaluated as a part of on-going prospective study on neonatal adverse drug reactions. Data on 456 neonates admitted to the Neonatal Intensive Care Unit were analyzed. Of these, 105 babies (23%) had TPN(glucose, amigen, intralipid) for 3024 days with a mean TPN duration of 28.3 days per patient (range 1174 d). TPN was started at age 5.1 d (range 1-48) for GI abnormalities (33.3%,e.g. necrotizing enterocolitis omphalocoele), severe prematurity (13.3%) and respiratory disorders (39.0%). 96 neonates survived (91.4%). 7 had a total of 9 central venous lines. The average weight gain per day was 8.36 g (range- 35 to 30.5 g). Hyperglycemia (>150 mg/dl, peak 695 mg/dl) occurred in 28 babies (26.7%), glycosuria in 19.0% and significant lipidemia in 18.1%. Abnormal liver function tests and liver disease were noted in 20 babies (19.0%); due to cytomegalovirus in one with no definitive cause in the others. 324 skin necrosis or sloughs (>0.5 cm) occurred in 71 babies (67.6%) while on TPN. 2 neonates developed severe trace metal deficiency, 1 died. Data underscore need for close surveillance and improvement of TPN techniques in the neonate.

Diagnosis of trace metal deficiency—with emphasis on copper and zinc

A method of diagnosing trace metal deficiency is proposed. Measurement of an appropriate metalloprotein before and after administration of a physiological replenishment dose of the metal should distinguish low levels due to metal deficiency from those due to other mechanisms. Serum ceruloplasmin is the logical protein for copper assessment; serum alkaline phosphatase and red cell carbonic anhydrase should be considered for zinc.